The mechanism(s) of tolerance induction in T and B cells will be studied in detail in isolated cell populations, and in model systems in which essentially all cells interact with a specific "tolerogen". In the former case, T and B cells from fluorescent tolerogen-injected animals will be purified by affinity chromatography, for example, in which specific antibody to fluorescein is attached to columns and cells bearing tolerance are removed and analyzed. Further studies on the interaction of lymphocytes with inhibitory doses of Concanavalin A and other lectins will be continued in the second model. Both systems will be followed in kinetic studies to determine the early membrane events in tolerance induction to an antigen or a lectin. The manipulation of tolerance in vivo and in vitro will also be studied in adoptive transfer systems in which the recipients are challenged with hapten-carrier protein conjugates. Unresponsiveness in T cells will then be evaluated in terms of carrier function, and B cell tolerance measured by the effect on hapten-specific plaque forming cell precursors. The involvement and role of "suppressor cells" in tolerance and the control of autoimmunity will be evaluated. Finally we will use these systems to study the nature of T vs. B cell receptors, the fate of "tolerant" cells and the reversal of immunity by carrier tolerance. These studies should aid in our understanding of the immune response and in our ability to activate and "turn off" immunocompetent cells in various disease states, for example, allergy and autoimmunity. BIBLIOGRAPHIC REFERENCES: Scott, D.W.: Isolation of Immunocompetent Lymphocytes with Anti-Fluorescein Affinity Columns. Fed. Proc. 35: in press, 1976. Long, C.A. and Scott, D.W.,: Induction of Tolerance with Haptenated Syngeneic Cells and Cell Supernatents. Fed. Proc. "35:" in press, 1976.